Table 1.

Investigational therapies for food-induced anaphylaxis that target IgE or its pathway components.

Specific agents by target	Mechanism of action	Advantages	Disadvantages
IgE and FcϵRI
Omalizumab* (anti-IgE mAb)	Prevents IgE binding to FcϵRI	Most well-studied potential therapy; favorable safety profile for chronic use; may facilitate food oral immunotherapy	Slow onset of action; incomplete prevention of clinical reactivity; most effective at lower serum IgE levels
Ligelizumab (anti-IgE mAb)	Prevents IgE binding to FcϵRI; may reduce B cell production of IgE	Higher affinity for IgE than omalizumab; favorable safety profile; may be more effective than omalizumab at high serum IgE levels	Moderately slow onset of action
Lumiliximab (anti-CD23)	Reduces B cell production of IgE	Long duration of total IgE reduction	Moderately slow onset of action
Quilizumab (anti-IgE mAb)	Depletes IgE-producing B cells	Long duration of total IgE reduction	Moderately slow onset of action
MEDI4212 (anti-IgE mAb)	Prevents IgE binding to FcϵRI; depletes IgE-producing B cells	May be more effective than omalizumab at high serum IgE levels	Moderately slow onset of action; shorter duration of action may mean more frequent dosing than omalizumab
E2_79 (anti-IgE darpin)	Prevents IgE binding to FcϵRI and dissociates existing complexes	Relatively rapid onset of action for dissociating IgE-FcϵRI complexes	No clinical data available
Kinases
Ibrutinib, acalabrutinib (BTK inhibitors)	Inhibition of FcϵRI signaling	Complete inhibition of FcϵRI signaling; rapid onset of action; oral dosing; next-generation inhibitors have favorable safety profile; shown to prevent systemic anaphylaxis in humanized mice	Side-effects may prevent chronic use
Fostamatinib**  (Syk inhibitor)	Inhibition of FcϵRI signaling	Rapid onset of action; oral dosing	Less favorable safety profile compared to other kinase inhibitors
GSK2646264  (Syk inhibitor)	Inhibition of FcϵRI signaling	Rapid onset of action	Currently in topical formulation only with unknown efficacy with oral dosing
WZ3146  (Lyn and Fyn inhibitor)	Inhibition of FcϵRI signaling	Rapid onset of action	No clinical data available; inhibitors may have increased toxicity due to broad enzyme expression
SHP and SHIP-1
Anti-CD32b/FcϵRI mAb or fusion proteins	Inhibition of FcϵRI signaling		No clinical data available; risk of inducing anaphylaxis
Allergen-specific IgG	Inhibition of FcϵRI signaling; competitive binding of allergen away from IgE		Allergen-dependent mechanism
Anti-CD300a mAb IE1 (anti-CD300a/IgE bispecific Ab)	Inhibition of FcϵRI signaling		No clinical data available; only partial reduction of degranulation in vitro
AQX-1125	Inhibition of FcϵRI signaling	Oral dosing	Only partial reduction of degranulation in vitro
Siglecs
Lirentelimab (AK002; anti-Siglec-8 mAb)	Inhibition of FcϵRI signaling	Target receptor has limited expression; favorable safety profile; shown to prevent systemic anaphylaxis in humanized mice; also depletes eosinophils
Dual targeting liposomes (antigen and anti-Siglec-3/CD33)	Inhibition of FcϵRI signaling	Shown to prevent systemic anaphylaxis in mice	No clinical data available; allergen-dependent mechanism
Anti-Siglec-6 mAb	Inhibition of FcϵRI signaling	Target receptor is exclusive to mast cells	No clinical data available; only partial reduction of degranulation in vitro
Anti-Siglec-7 mAb	Inhibition of FcϵRI signaling		No clinical data available; less effective in preventing basophil activation in vitro

*FDA-approved for asthma and CSU.

**FDA-approved for chronic refractory immune thrombocytopenic purpura.

All agents act in an allergen-independent mechanism unless otherwise noted.